• 1
    Lazaridis KN, Gores GJ. Our new president–Nicholas F. LaRusso, MD. Gastroenterology 2007; 132: 2005-2011.
  • 2
    de Duve C. Singularities: Landmarks on the Pathways of Life. Cambridge, UK: Cambridge University Press; 2005.
  • 3
    Sesna F. Middlebury College (Middlebury, VT) Commencement Speech. 1996.
  • 4
    LaRusso NF, Hoffman NE, Hofmann AF, Northfield TC, Thistle JL. Effect of primary bile acid ingestion on bile acid metabolism and biliary lipid secretion in gallstone patients. Gastroenterology 1975; 69: 1301-1314.
  • 5
    LaRusso NF, Szczepanik PA, Hofmann AF. Effect of deoxycholic acid ingestion on bile acid metabolism and biliary lipid secretion in normal subjects. Gastroenterology 1977; 72: 132-140.
  • 6
    LaRusso NF, Hoffman NE, Hofmann AF, Korman MG. Validity and sensitivity of an intravenous bile acid tolerance test in patients with liver disease. N Engl J Med 1975; 292: 1209-1214.
  • 7
    van Berge Henegouwen GP, Tangedahl TN, Hofmann AF, Northfield TC, LaRusso NF, McCall JT. Biliary secretion of copper in healthy man: quantitation by an intestinal perfusion technique. Gastroenterology 1977; 72: 1228-1231.
  • 8
    LaRusso NF, Fowler S. Coordinate secretion of acid hydrolases in rat bile: Hepatocyte exocytosis of lysosomal protein? J Clin Invest 1979; 64: 948-954.
  • 9
    LaRusso NF, Summerskill WHJ, McCall JC. Abnormalities of chemical tests for copper metabolism in chronic active liver disease: differentiation from Wilson's disease. Gastroenterology 1976; 70: 653-655.
  • 10
    Sewell RB, Barham SS, LaRusso NF. Effect of chloroquine on the form and function of hepatocyte lysosomes: morphologic modifications and physiologic alterations related to the biliary excretion of lipids and proteins. Gastroenterology 1983; 85: 1146-1153.
  • 11
    Novikoff PM, LaRusso NF, Novikoff AB, Stockert RJ, Yam A, LeSage GD. Immunocytochemical localization of lysosomal β-galactosidase in rat liver. J Cell Biol 1983; 97: 1559-1565.
  • 12
    Gores GJ, LaRusso NF, Miller LJ. Hepatic processing of cholecystokinin peptides: I. Structural specificity and mechanism of hepatic extraction. Am J Physiol 1986; 250: G344-G349.
  • 13
    Gores GJ, Miller LJ, LaRusso NF. Hepatic processing of cholecystokinin peptides: II. Cellular metabolism, transport, and biliary excretion. Am J Physiol 1986; 250: G350-G356.
  • 14
    LeSage GD, Kost LJ, Barham SS, LaRusso NF. Biliary excretion of iron from hepatocyte lysosomes in the rat: a major excretory pathway in experimental iron overload. J Clin Invest 1986; 77: 90-97.
  • 15
    Sewell RB, Grinpukel SA, Zinsmeister AR, LaRusso NF. Pharmacologic perturbation of rat liver lysosomes: effects on release of lysosomal enzymes and of lipids into bile. Gastroenterology 1988; 95: 1088-1098.
  • 16
    Gross JB, Myers BM, Kost LJ, Kuntz SM, LaRusso NF. Biliary copper excretion by hepatocyte lysosomes in the rat: major excretory pathway in experimental copper overload. J Clin Invest 1989; 83: 30-39.
  • 17
    Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 1980; 79: 200-206.
  • 18
    Quigley EM, LaRusso NF, Ludwig J, MacSween RNM, Birnie GG, Watkinson G. Familial occurrence of primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 1983; 85: 1160-1165.
  • 19
    MacCarty RL, LaRusso NF, Wiesner RH, Ludwig J. Primary sclerosing cholangitis: Findings on cholangiography and pancreatography. Radiology 1983; 149: 39-44.
  • 20
    Wiesner RH, LaRusso NF, Ludwig J, Dickson ER. Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. Gastroenterology 1985; 88: 108-114.
  • 21
    Gross JB, Ludwig J, Wiesner RH, McCall JT, LaRusso NF. Abnormalities in tests of copper metabolism in primary sclerosing cholangitis. Gastroenterology 1985; 89: 272-278.
  • 22
    MacCarty RL, LaRusso NF, May GR, Bender CE, Wiesner RH, King JE, Coffey RJ. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology 1985; 156: 43-46.
  • 23
    Wiesner RH, LaRusso NF, Dozois RR, Beaver SJ. Peristomal varices after proctocolectomy in patients with primary sclerosing cholangitis. Gastroenterology 1986; 90: 316-322.
  • 24
    Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J, MacCarty RL, Dozois RR, Zinsmeister AR, et al. Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology 1989; 96: 790-794.
  • 25
    Wiesner RH, Grambsch P, Dickson ER, Ludwig J, McCarty R, Hunter EB, Fleming TR, et al. Primary sclerosing cholangitis: natural history, prognostic factors, and survival analysis. HEPATOLOGY 1989; 10: 430-436.
  • 26
    Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg 1991; 213: 21-25.
  • 27
    Hay JE, Lindor KD, Wiesner RH, Dickson ER, Krom RAF, LaRusso NF. The metabolic bone disease of primary sclerosing cholangitis. HEPATOLOGY 1991; 14: 257-261.
  • 28
    Sandborn JW, Wiesner RH, Tremaine WJ, LaRusso NF. Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. Gut 1993; 34: 242-246.
  • 29
    Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19–9 in the diagnosis of cholangiocarcinoma in patients without primary sclerosing cholangitis. Gastroenterology 2000; 95: 204-207.
  • 30
    LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL, Beaver SJ, Zinsmeister AR. Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology 1988; 95: 1036-1042.
  • 31
    Lazaridis KN, Strazzabosco M, LaRusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology 2004; 127: 1565-1577.
  • 32
    Ishii M, Vroman B, LaRusso NF. Isolation and morphologic characterization of bile duct epithelial cells from normal rat liver. Gastroenterology 1989; 97: 1236-1247.
  • 33
    Roberts SK, Kuntz SM, Gores GJ, LaRusso NF. Regulation of bicarbonate-dependent ductular bile secretion assessed by lumenal micropuncture of isolated rodent intrahepatic bile ducts. Proc Natl Acad Sci U S A 1993; 90: 9080-9084.
  • 34
    Tietz PS, Holman RT, Miller LJ, LaRusso NF. Isolation and characterization of rat cholangiocyte vesicles enriched in apical or basolateral plasma membrane domains. Biochemistry 1995; 34: 15436-15443.
  • 35
    Vroman B, LaRusso NF. Development and characterization of polarized primary cultures of rat intrahepatic bile duct epithelial cells. Lab Invest 1996; 74: 303-313.
  • 36
    Tietz P, Levine S, Holman R, Fretham C, LaRusso NF. Characterization of apical and basolateral plasma membrane domains derived from cultured rat cholangiocytes. Anal Biochem 1997; 254: 192-199.
  • 37
    Ludwig J, Ritman EL, LaRusso NF, Sheedy PF, Zumpe G. Anatomy of the human biliary system studied by quantitative computer-aided three-dimensional imaging techniques. HEPATOLOGY 1998; 27: 893-899.
  • 38
    de Groen PC, Vroman B, Laakso K, LaRusso NF. Characterization and growth regulation of a rat intrahepatic bile duct epithelial cell line under hormonally defined, serum-free conditions. In Vitro Cell Dev Biol Anim 1998; 34: 704-710.
  • 39
    Masyuk AI, Gong AY, Kip S, Burke MJ, LaRusso NF. Perfused rat intrahepatic bile ducts secrete and absorb water, solute, and ions. Gastroenterology 2000; 119: 1672-1680.
  • 40
    Masyuk TV, Ritman EL, LaRusso NF. Quantitative assessment of the rat intrahepatic biliary system by three-dimensional reconstruction. Am J Pathol 2001; 158: 2079-2088.
  • 41
    Ueno Y, Phillips JO, Ludwig J, Lichtman SN, LaRusso NF. Development and characterization of a rodent model of immune-mediated cholangitis. Proc Natl Acad Sci U S A 1996; 93: 216-220.
  • 42
    Cova E, Gong A, Marinelli RA, LaRusso NF. Water movement across rat bile duct units is transcellular and channel-mediated. HEPATOLOGY 2001; 34: 456-463.
  • 43
    Ishii M, Vroman B, LaRusso NF. Morphologic demonstration of receptor-mediated endocytosis of epidermal growth factor by isolated bile duct epithelial cells. Gastroenterology 1990; 98: 1284-1291.
  • 44
    Kato A, Gores GJ, LaRusso NF. Secretin stimulates exocytosis in isolated bile duct epithelial cells by a cyclic AMP-mediated mechanism. J Biol Chem 1992; 267: 15523-15529.
  • 45
    Roberts SK, Yano M, Ueno Y, Pham L, Alpini G, Agre P, LaRusso NF. Cholangiocytes express aquaporin CHIP and transport water via a channel-mediated mechanism. Proc Natl Acad Sci U S A 1994; 91: 13009-13013.
  • 46
    Tietz PS, Alpini G, Pham LD, LaRusso NF. Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by cholangiocytes. Am J Physiol 1995; 269: G110-G118.
  • 47
    Tan CK, Podila PV, Taylor JE, Nagorney DM, Wiseman GA, Gores GJ, LaRusso NF. Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition. Gastroenterology 1995; 108: 1908-1916.
  • 48
    Alpini G, Ulrich C, Roberts S, Phillips JO, Ueno Y, Podila PV, Colegio O, et al. Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation. Am J Physiol 1997; 272: G289-G297.
  • 49
    Marinelli R, Pham L, Agre P, LaRusso NF. Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane: Evidence for a secretin-induced vesicular translocation of aquaporin-1. J Biol Chem 1997; 272: 12984-12988.
  • 50
    Lazaridis KN, Pham L, Tietz P, Marinelli RA, de Groen PC, Levine S, Dawson PA, et al. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter. J Clin Invest 1997; 100: 2714-2721.
  • 51
    Marinelli RA, Tietz PS, Pham LD, Rueckert L, Agre P, LaRusso NF. Secretin induces the apical insertion of aquaporin-1 water channels in rat cholangiocytes. Am J Physiol 1999; 276: G280-G286.
  • 52
    Chen XM, LaRusso NF. Mechanisms of attachment and internalization of Cryptosporidium parvum to biliary and intestinal epithelial cells. Gastroenterology 2000; 118: 368-379.
  • 53
    Marinelli RA, Pham LD, Tietz PS, LaRusso NF. Expression of aquaporin-4 water channels in rat cholangiocytes. HEPATOLOGY 2000; 31: 1313-1317.
  • 54
    Chen XM, Levine SA, Splinter PL, Tietz PS, Ganong AL, Jobin C, Gores GJ, et al. Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis. Gastroenterology 2001; 120: 1774-1783.
  • 55
    Gong AY, Masyuk AI, Splinter PL, Huebert RC, Tietz PS, LaRusso NF. Channel-mediated water movement across enclosed or perfused mouse intrahepatic bile duct units. Am J Physiol 2002; 283: C338-C346.
  • 56
    Masyuk AI, Masyuk TV, Tietz PS, Splinter PL, LaRusso NF. Intrahepatic bile ducts transport water in response to absorbed glucose. Am J Physiol 2002; 283: C785-C791.
  • 57
    Gong AY, Tietz PS, Muff MA, Splinter PL, Huebert RC, Strowski MZ, Chen XM, et al. Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes. Am J Physiol 2003; 184: C1205-C1214.
  • 58
    Tietz PS, Marinelli RA, Chen XM, Cohn J, Kole J. McNiven MA, LaRusso NF. Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. J Biol Chem 2003; 278: 20413-20419.
  • 59
    Chen XM, Huang BQ, Splinter PL, Cao H, Zhu Z, McNiven MA, LaRusso NF. Cryptosporidium parvum invasion of biliary epithelia requires host-cell tyrosine phosphorylation of cortactin via c-Src. Gastroenterology 2003; 125: 216-228.
  • 60
    Marinelli RA, Tietz PS, Caride AJ, Huang BQ, LaRusso NF. Water transporting properties of hepatocyte, basolateral and canalicular plasma membrane domains. J Biol Chem 2003; 278: 43157-43162.
  • 61
    Splinter PL. Masyuk AI, Marinelli RA, LaRusso NF. AQP4 transfected into mouse cholangiocytes promotes water transport in biliary epithelia. HEPATOLOGY 2004; 39: 109-116.
  • 62
    Chen XM, Splinter PL, Tietz PS, Huang BQ, Billadeau DD, LaRusso NF. Phosphatidylinositol 3 kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of Cdc42. J Biol Chem 2004; 279: 31671-31678.
  • 63
    Chen XM, O'Hara SP, Huang BQ, Splinter PL, Nelson JB, LaRusso NF. Localized glucose and water influx facilitates cryptosporidium parvum cellular invasion by means of modulation of host-cell membrane protrusion. Proc Natl Acad Sci U S A 2005; 102: 6338-6343.
  • 64
    Tietz P, Jefferson J, Pagano R, LaRusso NF. Membrane microdomains in hepatocytes: potential target areas for proteins involved in canalicular bile secretion. J Lipid Res 2005; 46: 1426-1432.
  • 65
    Chen XM, O'Hara SP, Nelson JP, Splinter PL, Small AJ, Tietz PS, Limper AH, et al. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation in NF-kB. J Immunol 2005; 175: 7447-7456.
  • 66
    Mazzone A, Tietz PS, Jefferson JJ, Pagano R, LaRusso NF. Isolation and characterization of lipid microdomains from apical and basolateral plasma membranes of rat hepatocytes. H Epatology 2006; 43: 287-296.
  • 67
    Masyuk TV, Huang BQ, Ward CJ, Masyuk AI, Yuan D, Splinter PL, Punyashthiti R, et al. Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat. Gastroenterology 2003; 125: 1303-1310.
  • 68
    Huang BQ, Masyuk TV, Muff MA, Tietz PS, Masyuk AI, LaRusso NF. Isolation and characterization of cholangiocyte primary cilia. Am J Physiol 2006; 291: G500-G509.
  • 69
    Masyuk AI, Masyuk TV, Splinter PL, Huang BQ, Stroope AJ, LaRusso NF. Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 2006; 131: 911-920.
  • 70
    Masyuk TV, Masyuk AI, Torres VE, Harris PC, LaRusso NF. Octreotide inhibits hepatic cystogenesis and fibrosis by reduction of cholangiocyte cAMP: a potential therapeutic approach for the polycystic liver diseases. Gastroenterology 2007; 132: 1104-1116.
  • 71
    Gradilone SA, Masyuk AI, Splinter PL, Banales JM, Huang BQ, Tietz PS, Masyuk TV, et al. Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity including bicarbonate secretion. Proc Natl Acad Sci, U S A 2007; 104: 19138-19143.
  • 72
    Masyuk AI, Gradilone SA, Banales JM, Huang BQ, Masyuk TV, Lee SO, Splinter PL, et al. Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol 2008; 295: G725-G734.
  • 73
    Banales JM, Masyuk TV, Gradilone SA, Masyuk AI, Medina JF, LaRusso NF. The cAMP effectors EPAC and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). HEPATOLOGY 2009; 49: 160-174.
  • 74
    Gradilone SA, Masyuk TV, Huang BQ, Banales JM. Lehmann GL, Radtke BN, Stroope A, et al. Activation of Trpv4 reduces the hyperproliferative phenotype of cystic cholangiocytes from an animal model of ARPKD. Gastroenterology 2010; 139: 304-314.
  • 75
    Masyuk AI, Huang BQ, Ward CJ, Gradilone SA, Banales JM, Masyuk TV, Radtke B, et al. Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am J Physiol 2010; 299: G990-G999.
  • 76
    Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, Kim B, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol 2010; 21: 1052-1061.
  • 77
    Splinter PL, Masyuk AI, LaRusso NF. Specific inhibition of AQP1 water channels in isolated rat intrahepatic bile duct units by small interfering RNAs. J Biol Chem 2003; 278: 6268-6274.
  • 78
    Chen XM, Splinter PL, O'Hara SP, LaRusso NF. A cellular miRNA, let-7i, regulates toll-like receptor 4 expression and contributes to cholangiocyte immune response against cryptosporidium parvum infection. J Biol Chem 2007; 282: 28929-28938.
  • 79
    Lee SO, Masyuk TV, Splinter PL, Masyuk AI, Stroope AJ, LaRusso NF. MicroRNA-15a regulates the expression of the cell-cycle regulator cdc25a affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest 2008; 118: 3714-3724.
  • 80
    O'Hara SP, Splinter PL, Gajdos GB, Trussoni CE, Fernandez-Zapico ME, Chen XM, LaRusso NF. NFκB p50-CCAAT/enhancer-binding protein β (C/EBPβ)-mediated transcriptional repression of microRNA let-7i following microbial infection. J Biol Chem 2010; 285: 216-225.